A Phase 1b Dose Escalation Evaluation of Safety and Tolerability and a Phase 2 Proof of Concept Investigation of Efficacy and Safety of ASP7317 for Atrophy Secondary to Age-related Macular Degeneration


Original post, click here
Primary Outcome Measures:

  • PoC only: Change from baseline in BCVA, measured by ETDRS method, average of assessments from weeks 4 to 26 [ Time Frame: Baseline and up to Week 26 ]

    Best corrected visual acuity (BCVA) will be measured by an assessor certified to use the early treatment of diabetic retinopathy study (ETDRS) method. Total number of letters read correctly will be reported.

  • Safety as assessed by Incidence, frequency and severity of adverse events (AEs) [ Time Frame: Up to 60 Months ]

    Adverse events (AEs) will be coded using Medical Dictionary for Regulatory Activities (MedDRA). Adverse event collection will begin upon the participant signing the informed consent.

  • Number of Participants with graft failure or rejection [ Time Frame: Up to 60 Months ]

    Evidence of graft failure or rejection will be assessed by BCVA, slit lamp examination, dilated indirect ophthalmoscopy, fundus photographs, spectral domain-optical coherence tomography (SD-OCT) and fluorescein angiography (FA), when performed.

  • Number of Participants with clinically significant changes in laboratory tests [ Time Frame: Up to 26 Weeks ]

    An abnormality identified during a medical test will be defined as an AE only if the abnormality meets 1 of the following criteria: induces clinical signs or symptoms; requires active intervention; requires interruption or discontinuation of adjunct study medications; age-related eye disease studies (AREDS) lens grade increase from baseline by ≥ 1 grade; the abnormality or test value is clinically significant; visual acuity loss of ≥ 10 letters due to graft failure or rejection.

  • Number of Participants with clinically significant changes in blood pressure [ Time Frame: Up to 12 Weeks ]

    Clinically significant changes in blood pressure will be reported as moderate or severe.

  • Number of Participants with clinically significant changes in intraocular pressure (IOP) in each eye [ Time Frame: Up to 60 Months ]

    Intraocular pressure in both eyes will be measured by tonometry. Intraocular pressure should be measured after biomicroscopic examination and before pupil dilation approximately the same time of day, when possible.

Secondary Outcome Measures:

  • PoC only: Change from baseline in BCVA at week 26 [ Time Frame: Baseline and Week 26 ]

    BCVA will be measured by an assessor certified to use the ETDRS method. Total number of letters read correctly will be reported.

  • PoC only: Proportion of participants with confirmed ≥ 15 letter improvement in BCVA at week 26 [ Time Frame: Baseline and Week 26 ]

    BCVA will be measured by an assessor certified to use the ETDRS method.

  • PoC only: Change from baseline in mean retinal sensitivity of the perilesional points by microperimetry at week 26 [ Time Frame: Baseline and Week 26 ]

    Microperimetry will be performed at all sites using a macular integrity assessment (MAIA) microperimeter.

  • PoC only: Change from baseline in area of definite decreased autofluorescence (DDAF) at week 26 [ Time Frame: Baseline and Week 26 ]

    DDAF will be assessed by Fundus Autofluorescence Photography (FAF). The image reading center will review the FAF images for area of DDAF and pattern of hyper autofluorescence around the DDAF.

This is a two stage study followed by an extension and a safety surveillance period. Stage 1 is a Phase 1b dose escalation evaluation of 3 doses of ASP7317 and Stage 2 is Phase 2 Proof of Concept (PoC) investigation.

During the dose escalation stage participants will be treated in each of the 3 dose cohorts (low cells/dose; medium cells/dose; high cells/dose). Doses will be administered to the study eye via a subretinal injection. Four weeks after the last participant in each dose cohort is treated, the independent Data Safety Monitoring Board (DSMB) will review data and images. Depending on the safety data there will be a recommendation to proceed to the next higher dose; stop dose escalation; investigate a lower dose or repeat a dose level.

The PoC stage will begin immediately following the recommendation of the DSMB and the Dose Escalation Committee (DEC) on the selected dose. Participants will be randomized in a 1:1:1 ratio to either the low cells/dose; the selected cells/ dose or an untreated control group. Doses will be administered to the study eye via a subretinal injection for the low cells/ dose and the selected cells/ dose.

All participants treated with ASP7317 in the Dose Escalation and PoC stage will receive 13 weeks of immunosuppressive therapy (IMT) starting 1 week prior to day of transplant and continuing for 12 weeks post-transplant.

If the primary outcome for PoC is demonstrated for the low cells/ dose and the selected cells/dose then participants in the untreated control group who completed the 26 week visit, continue to meet the eligibility criteria and are suitable for immunosuppression therapy are allowed to cross over to treatment with ASP7317.

At the last study visit or time of withdrawal participants receiving ASP7317 will be consented to participate in the safety surveillance period of the study, which will continue to monitor the participants for long-term safety via an annual questionnaire.